Triethylamine → HCID 15291044, compound

HRID 1067872Notes

Reaction equation

HRID 1067872 reaction equation
[CH3:1][CH:2]([C@H:4]([NH:8][C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10])[C:5]([OH:7])=O)[CH3:3].C(N(CC)CC)C.C(Cl)(=O)C(C)(C)C.[NH2:33][C@H:34]([C:38]([N:40]([CH3:56])[C@H:41]([C:45]([N:47]1[CH2:55][CH2:54][CH2:53][C@H:48]1[C:49]([O:51][CH3:52])=[O:50])=[O:46])[CH:42]([CH3:44])[CH3:43])=[O:39])[CH:35]([CH3:37])[CH3:36]>C(Cl)Cl.O>[NH:8]([C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10])[C@H:4]([C:5]([NH:33][C@H:34]([C:38]([N:40]([CH3:56])[C@H:41]([C:45]([N:47]1[CH2:55][CH2:54][CH2:53][C@H:48]1[C:49]([O:51][CH3:52])=[O:50])=[O:46])[CH:42]([CH3:44])[CH3:43])=[O:39])[CH:35]([CH3:36])[CH3:37])=[O:7])[CH:2]([CH3:1])[CH3:3]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 726987N-Carbobenzoxy-L-valineHCID 15291043HCID 15291043, compound

Product 1

HCID 15291044HCID 15291044, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
20 °C

Procedure

17.84 kg (70.88 mol) of Z-valine and 4.59 kg (74.42 mol) of tri-ethylamine were dissolved in 170 l of methylene chloride in a 400 l vessel. To this solution were added at −5 to −10° C. 8.58 kg (70.88 mol) of pivaloyl chloride. After a reaction time of 2 h at −5° C., a solution of 24.2 kg of Val-MeVal-Pro-OMe in 86 l of methylene chloride was run in at −5° C. After a further 2 h at −5° C., the mixture was heated to 20° C. and stirred at this temperature for 12 h. 50 l of water were added for working up. After removal of the aqueous phase, the organic phase was extracted once with 40 l of 2N hydrochloric acid and twice with 40 1 of 2N sodium hydroxide solution each time. The organic phase was washed until neutral and then the methylene chloride solvent was removed by distillation and replaced by 300 l of diisopropyl ether. The product was crystallized by heating the emulsion of the oily product to 60° C., adding seed crystals and keeping at 60° C. for 7 h. To complete the crystallization, the mixture was stirred further at 50° C. for 5 h and then at 40° C. for 5 h and subsequently cooled to 20° C. The suspension of crystals was discharged through a 120 l pressure filter.

Workup

  1. additionTo this solution were added at −5 to −10° C
  2. customAfter a reaction time of 2 h
  3. customat −5° C.
  4. customwas run in at −5° C
  5. customAfter removal of the aqueous phase
  6. extractionthe organic phase was extracted once with 40 l of 2N hydrochloric acid and twice with 40 1 of 2N sodium hydroxide solution each time
  7. washThe organic phase was washed until neutral and then the methylene chloride solvent
  8. customwas removed by distillation
  9. customThe product was crystallized
  10. temperatureby heating the emulsion of the oily product to 60° C.
  11. additionadding seed crystals
  12. waitkeeping at 60° C. for 7 h
  13. customthe crystallization
  14. stirringthe mixture was stirred further at 50° C. for 5 h
  15. waitat 40° C. for 5 h
  16. temperaturesubsequently cooled to 20° C
  17. additionThe suspension of crystals
  18. filtrationfilter

Sources & evidence

ORD record
ord-55c9e11238b54bc9a80c5945eeff902d
Source dataset
uspto-grants-2001_06
Patent number
US06248865B1

Reaction notes

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